Kenton
M. Sanders, Ph. D.
Professor
and Chairman

I
have been interested in smooth muscle physiology and pharmacology
for most of my career. As a student, I became interested in electrical
rhythmicity in gastrointestinal (GI) smooth muscles, and I have
devoted most of my efforts to trying to understand the mechanisms
responsible for this activity. Like the heart, many GI smooth
muscles have spontaneous rhythmicity. We now think that a special
class of pacemaker cells, interstitial cells of Cajal (ICC), drives
this activity. I have collaborated with Dr. Sean Ward for several
years on the study of ICC. We have used electrophysiology, optical
imaging techniques, molecular biology, confocal and electron microscopy,
and several other techniques to study the structure and function
of ICC. These cells are present in pacemaker areas of the GI tract.
ICC are excitable cells that are spontaneously active after dispersing
from intact muscles. The rhythmicity of GI muscles stops when
ICC are damaged or lost. We are currently studying the development
of ICC and trying to understand what happens to these cells in
certain types of GI motility disorders. Look at our reviews in
Gastroenterology (Vol. 111:492-515, 1996) or Neurogastroenterology
and Motility (Vol. 11:311-38, 1999). if you want to learn more
about ICC and the progress that has been made on these cells.
I've
also been interested in neural control of GI muscles. GI muscles
are controlled by excitatory and inhibitory motor neurons, and
we have spent considerable effort trying to understand how the
transmitter substances released by these neurons affect electrical
rhythmicity, intracellular calcium, and contraction. One of the
most exciting advances that has occurred during the past decade
is the finding that nitric oxide serves as a primary neurotransmitter
in visceral tissues. This substance is of great importance in
GI muscles, and we have looked into many aspects of the role of
nitric oxide as a neurotransmitter. Recently we have been working
on how ATP (another inhibitory transmitter) activates potassium
channels in GI muscles. This occurs by localized calcium release
and activation of small-conductance calcium-activated potassium
channels. We also now recognize that ICC are fundamental for neurotransmission
in GI muscles, and loss of these cells can impair both excitatory
and inhibitory neural inputs.
Much
of our work on the role of neurotransmitters has focused on how
these substances affect the ionic conductances that are responsible
for electrical excitability. We have used the patch clamp technique
extensively for these studies, but now we are also using molecular
biological techniques in collaboration with Dr.
Seungil Ro, to study more basic aspects of transmitter regulation
of ion channels.
Search
For Dr. Sanders' Publications In PubMed
Selected
Publications
--
Langton, P.D., S. Ward, M. Norell and K.M. Sanders.
(1989) Spontaneous electrical activity from interstitial cells
of Cajal isolated from canine proximal colon. Proc. Nat.
Acad. Sci. 86:7280-7284.
-- Thornbury, K.D., S.M. Ward, H.H. Dalziel, A. Carl, D.P. Westfall
and K.M. Sanders. (1991) Nitric oxide and nitrosocysteine
mimic non-adrenergic, non-cholinergic hyperpolarization in gastrointestinal
muscles. Am. J. Physiol. 261:G553-G557.
-- Lee, H.K. and K.M. Sanders. (1993) Comparison
of ionic currents from interstitial cells and smooth muscle cells
of canine colon. Journal of Physiology 460:135-152.
-- Publicover, N.G., E.M. Hammond and K.M. Sanders.
(1993) Amplification of nitric oxide signalling by interstitial
cells. Proc. Nat. Acad. Sci. 90:2087-2091.
-- Ward, S.M., A.J. Burns, S. Torihashi and K.M. Sanders.
(1994) Mutation of the proto-oncogene c-kit blocks development
of interstitial cells and electrical rhythmicity in the murine
intestine. J. Physiology (Rapid Communication).
480:91-97.
-- Burns, A.J., A.E.J. Lomax, S. Torihashi, K.M. Sanders
and S.M. Ward. (1996) Interstitial cells of Cajal mediate inhibitory
neurotransmission in the stomach. Proc. Nat. Acad. Sci.
(USA) 93:12008-12013.
-- Torihashi S., K. Nishi, Y. Tokutomi, T. Nishi, S.M. Ward and
K.M. Sanders (1999) Blockade of Kit signaling
induces transdifferentiation of interstitial cells of Cajal to
a smooth muscle phenotype. Gastroenterology.
117: 140-148.
-- Ördög, T., I. Takayama, W.K.T. Cheung, S.M. Ward
and K.M. Sanders. (2000) Remodeling of networks
of interstitial cells of Cajal in diabetic gastroparesis. Diabetes.
49: 1731-1739.
-- Ward, S.M., E.A.H. Beckett, X-Y. Wang, F. Baker, M. Khoyi and
K.M. Sanders. (2000) Interstitial cells of Cajal
mediate enteric excitatory neurotransmission in the murine fundus.
Journal of Neuroscience 20:1393-1403.
-- Ward, S.M., T. Ördög, S.D. Koh, S. Abu Baker, J.Y.
Jun, G. Amberg, K. Monaghan and K.M. Sanders.
(2000) Pacemaking in interstitial cells of Cajal depends upon
calcium handling by endoplasmic reticulum and mitochondria. Journal
of Physiology (Rapid Report) 525: 355-361.
-- Bayguinov, O, B. Hagen, A.D. Bonev, M.T. Nelson and K.M.
Sanders. (2000) Intracellular calcium events activated
by ATP in murine colonic myocytes. American Journal of
Physiology - Cell 279: C126-135.
-- Bayguinov, O, B. Hagen, J.L. Kenyon and K.M. Sanders.
(2001) Coupling strength between localized Ca2+ transients and
K+ channels is regulated by protein kinase C. American Journal
of Physiology: Cell Physiology. 281: C1512-1523.
-- Koh, S.D. and K.M. Sanders (2001) Stretch-dependent
potassium channels in murine and canine colonic smooth muscle
cells. Journal of Physiology 533: 155-163.
-- Dick, G.M. and K.M. Sanders. (2001) [Xeno]estrogen-sensitivity
of smooth muscle BK channels conferred by the regulatory ß1
subunit: A study of ß1 knockout mice. J Biological
Chemistry 276: 44835-44840.
-- Kim, Y.C., S.D. Koh and K.M. Sanders. (2002)
Voltage-dependent inward currents of interstitial cells of Cajal
from murine colon and small intestine. Journal of Physiology
541: 797-810.
-- Koh, S.D., J.Y. Jun, T.W. Kim and K.M. Sanders.
(2002) A Ca2+-inhibited non-selective cation conductance contributes
to pacemaker currents in cultured interstitial cells of Cajal.
Journal of Physiology 540: 803-814.
-- Ördög, T., M. Baldo, R. Danko and K.M. Sanders. (2002)
Plasticity of electrical pacemaking by interstitial cells of Cajal
underlies gastric dysrhythmia in W/WV mutant mice. Gastroenterology
123: 2028-2040.
-- Kim, T.W., S.D. Koh, T. Ördög and K.M. Sanders
(2003) Muscarinic regulation of pacemaker frequency in gastric
interstitial cells of Cajal. Journal of Physiology 546:
415-425.
-- Ward, S.M., S.A. Baker, A. de Faoite and K.M. Sanders.
(2003) Propagation of slow waves requires regeneration via IP3
receptors and mitochondrial Ca2+ uptake mechanism in canine colonic
muscles. Journal of Physiology 549: 207-218.
-- Hagen, B, O. Bayguinov and K.M. Sanders. (2003)
ß1 subunits are required for regulation of coupling between
Ca2+ transients and Ca2+ activated K+ (BK) channels by protein
kinase C. American Journal of Physiology - Cell Physiology
285: C1270-C1280.
-- Amberg, G.C., S.D. Koh, Y. Imaizumi, S. Ohya, and K.M.
Sanders. (2003) A-type potassium currents in smooth muscles.
American Journal of Physiology – Cell Physiology.
Invited Review. 284: C583-C595.
-- Ördög, T., Redelman, D., Miller, L.J., Horváth,
V.J., Zhong, Q., Graça Almeida-Porada, G., Zanjani, E.D.,
Horowitz, B. and Sanders, K.M. (2004) Purification
of interstitial cells of Cajal by fluorescence-activated cell
sorting. American Journal of Physiology: Cell Physiology
286: C448-456.
-- Won K-J, Sanders KM, Ward SM. (2005) Interstitial
cells of Cajal mediate mechano-sensitive responses in the stomach.
Proceedings of the National Academy of Science
(USA) 102: 14913-14918.
-- Cho SY, Beckett EA, Baker SA, Han I, Park KJ, Monaghan K, Ward
SM, Sanders KM, Koh SD. (2005) A pH-sensitive
potassium conductance (TASK) and its function in the murine gastrointestinal
tract. Journal of Physiology 565: 243-259.
-- Kito Y, Ward SM, Sanders KM. (2005) Pacemaker
potentials generated by interstitial cells of Cajal in the murine
intestine. American Journal of Physiology: Cell Physiology
288: C710-720.
-- Sanders KM, Koh SD, Ward SM. (2006) Interstitial
cells of Cajal as pacemakers in the gastrointestinal tract. Annual
Review of Physiology 68:307-343.
-- Sanders KM (2006) Interstitial cells of Cajal
at the clinical and scientific interface. Journal of Physiology
576:683-687.
-- Park KJ, Hennig GW, Lee H-T, Spencer NJ, Ward SM, Smith TK,
Sanders KM (2006) Spatial and temporal mapping
of pacemaker activity in interstitial cells of Cajal in mouse
ileum in situ. American Journal of Physiology: Cell Physiology
290:C1411-C1427.
-- Ward SM, Sanders KM (2006) Involvement of
intramuscular interstitial cells of Cajal in neuroeffector transmission
in the gastrointestinal tract. Journal of Physiology
576:675-682.
-- Chen H, Redelman D, Ro S, Ward SM, Ordog T, Sanders
KM (2007) Selective labeling and isolation of functional
classes of interstitial cells of Cajal of human and murine small
intestine. Am J Physiol Cell Physiol. 292:C497-507.
-- Sanders KM, Ward SM (2007) Kit mutants and
gastrointestinal physiology. Journal of Physiology
578:33-42.